Binding Model of Capsaicin is Able to Reach the Peripheral Anionic Site of Acetylcholinesterase

Author(s):

Abstract:

Background: Capsaicinoids content of peppers is one of the major parameters that determine its commercial and nutritional values. Despite their properties and application in the food industry, capsaicinoid compounds have been widely studied in the pharmaceutical area due to their therapeutic activities such as antioxidant, antimicrobial, antitumor, antiobesity, anti-inflammatory and analgesic effects.

Methods: Capsacin bioactivity prediction step was made with PharmMapper, SwissTargetPredicition and PASS online servers. After, docking simulations were performed for capsaicin and acetylcholinesterase with GOLD suite 4.12 inside a sphere of 17 Å centered at CZ atom of Phe331, where the 5 top-ranked poses were selected using the Chemscore function and a population size of 100, selection pressure of 1.1, 100,000 operations, number of islands of 5, niche size of 2, crossover frequency of 95, mutation frequency of 95 and migration frequency of 10.

Results: The bioactivity prediction data of capasaicin revealed a wide range of potential activities in humans, specially the interference in enzymes involved in metabolic reactions, anti-inflammatory and antineoplastic propensity, pain control and action on cholinergic transmission. Docking simulations with acetylcholinesterase showed that capsaicin may reach the enzyme peripheral anionic site, being a candidate capable of possibly avoiding the amyloid assembly step in Alzheimer’s disease.

Conclusion: The natural product capsaicin, extracted from chili peppers, presents a wide bioactivity spectrum. It is already used in clinical practice due to its potential benefits as an analgesic drug. The hypothesis of capsaicin acting as a neuroprotective agent against alzheimer’s disease seems to be logical once some bioactivity prediction tools reveal the possible action on mechanisms important for actual drugs, specially the inhibition of acetylcholinesterase. Capsaicin has a chemical structure able to reach the peripheral anionic site of the enzyme, being a potential candidate to influence amyloid deposition and induce a disease-modifying effect against Alzhemier’s disease.